Studies on recovery from chemically induced damage in mammalian cells

Abstract

The survival of plateau-phase or nondividing Chinese hamster ovary cells (in vitro) is reduced to a greater extent by treatments with nitrosourea compounds than are cells treated in the exponential phase of growth. The greatest decrease in the survival fraction occurred following treatments with 1-trans-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea where approximately 128 times more cells were killed in plateau phase than in the dividing state (at the 10 mug/ml-for-1-hr dose). Only 5 times more cells were killed in plateau phase than in exponential growth when cells were treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Cells treated with either nitrosourea compound failed to recover from potentially lethal damage and sublethal damage. The breakdown products of the nitrosourea compounds are known to inhibit DNA repair and may explain the failure of mammalian cells to recover from sublethal damage and potentially lethal damage induced by these chemicals. Both dividing and nondividing cells were able to recover from bleomycin-induced potentially lethal damage but not from sublethal damage. The recovery from bleomycin-induced potentially lethal damage by nondividing cells was twice as great as that exhibited by dividing cells; however, potentially lethal damage recovery was suffieiently high for cells in both growth states to conceal the true response to sublethal damage.